Predictive Value of C-reactive Protein for Hospitalization and Mortality Among People With Advanced HIV Disease in Uganda Receiving the World Health Organization-recommended Package of Care

Background People with advanced human immunodeficiency virus (HIV) disease (CD4 ≤ 200 cells/µL) remain at high risk for opportunistic infections, hospitalization, and death, despite access to antiretroviral therapy (ART). We evaluated serum C-reactive protein (CRP) as a predictor of 30-day hospitalization or death among outpatients with advanced HIV disease. Methods We prospectively enrolled 1388 outpatient Ugandan adults with CD4 ≤ 200 cells/µL from May 2022 to February 2025, of whom 1378 had serum CRP measured at enrollment. Participants were ART-naïve or experienced, and people with known virologic suppression were excluded. Participants received tuberculosis and cryptococcosis screening and therapy per World Health Organization (WHO) recommendations. We examined CRP as a continuous and dichotomized predictor (≥10 mg/L) of 30-day hospitalization or death. Results Among 1378 participants, 41.6% had CRP ≥10 mg/L. Participants with CRP ≥10 mg/L were more likely to be hospitalized (relative risk = 4.2, 95% CI: 2.3-7.8) or die (relative risk = 9.8, 95% CI: 2.9-32.8) within 30 days. In a multivariable Cox model adjusted for weight, CD4 count, ART status, and age, each 2-fold increase in CRP was associated with a 36.9% higher hazard of 30-day hospitalization or death (hazard ratio = 1.4, 95% CI: 1.2-1.5). Including CRP in the multivariable model significantly improved prediction of 30-day hospitalization or death (AUC 0.80 with CRP vs 0.72 without, DeLong's P = .009). Conclusions CRP ≥10 mg/L is associated with increased risk of 30-day hospitalization or death among outpatients with advanced HIV disease receiving the WHO-recommended package of care. Prospective studies should evaluate whether point-of-care CRP testing can enable real-time risk stratification to reduce AIDS-related deaths.